Document Detail

Differential effects of cystathionine-γ-lyase-dependent vasodilatory H2S in periadventitial vasoregulation of rat and mouse aortas.
MedLine Citation:
PMID:  22870268     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Hydrogen sulfide (H(2)S) is a potent vasodilator. However, the complex mechanisms of vasoregulation by H(2)S are not fully understood. We tested the hypotheses that (1) H(2)S exerts vasodilatory effects by opening KCNQ-type voltage-dependent (K(v)) K(+) channels and (2) that H(2)S-producing cystathionine-γ-lyase (CSE) in perivascular adipose tissue plays a major role in this pathway.
METHODOLOGY/PRINCIPAL FINDINGS: Wire myography of rat and mouse aortas was used. NaHS and 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) were used as H(2)S donors. KCNQ-type K(v) channels were blocked by XE991. 4-Propargylglycine (PPG) and ß-cyano-l-alanine (BCA), or 2-(aminooxy)-acetic acid (AOAA) were used as inhibitors of CSE or cystathionine-ß-synthase (CBS), respectively. NaHS and ADTOH produced strong vasorelaxation in rat and mouse aortas, which were abolished by KCNQ channel inhibition with XE991. Perivascular adipose tissue (PVAT) exerted an anticontractile effect in these arteries. CSE inhibition by PPG and BCA reduced this effect in aortas from rats but not from mice. CBS inhibition with AOAA did not inhibit the anticontractile effects of PVAT. XE991, however, almost completely suppressed the anticontractile effects of PVAT in both species. Exogenous l-cysteine, substrate for the endogenous production of H(2)S, induced vasorelaxation only at concentrations >5 mmol/l, an effect unchanged by CSE inhibition.
CONCLUSIONS/SIGNFICANCE: Our results demonstrate potent vasorelaxant effects of H(2)S donors in large arteries of both rats and mice, in which XE991-sensitive KCNQ-type channel opening play a pivotal role. CSE-H(2)S seems to modulate the effect of adipocyte-derived relaxing factor in rat but not in mouse aorta. The present study provides novel insight into the interaction of CSE-H(2)S and perivascular adipose tissue. Furthermore, with additional technical advances, a future clinical approach targeting vascular H(2)S/KCNQ pathways to influence states of vascular dysfunction may be possible.
Carolin Köhn; Johanna Schleifenbaum; István András Szijártó; Lajos Markó; Galyna Dubrovska; Yu Huang; Maik Gollasch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-03
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-08-07     Completed Date:  2013-02-19     Revised Date:  2013-08-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e41951     Citation Subset:  IM    
Medical Clinic for Nephrology and Internal Intensive Care, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
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MeSH Terms
Air Pollutants / pharmacology
Aorta / cytology,  enzymology*
Cystathionine gamma-Lyase / metabolism*
Cysteine / pharmacology
Hydrogen Sulfide / pharmacology*
Ion Channel Gating / drug effects
KCNQ Potassium Channels / metabolism
Potassium Channel Blockers / pharmacology
Rats, Sprague-Dawley
Vasodilation / drug effects*
Vasodilator Agents / pharmacology*
Reg. No./Substance:
0/Air Pollutants; 0/KCNQ Potassium Channels; 0/Potassium Channel Blockers; 0/Vasodilator Agents; 52-90-4/Cysteine; 7783-06-4/Hydrogen Sulfide; EC gamma-Lyase

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